Tamoxifen: Possible Drug Interactions and Alternatives

Posted on
8/01/11

by
Joanne M Faysal, MS, C (ASCP)

DH, a 65-year-old female, recently met with her pharmacist for her semi-annual medication therapy review session. DH’s daily medications are fluoxetine (40 mg) for depression, atorvastatin (80 mg) for hyperlipidemia, lisinopril (20 mg) for hypertension, and diphenhydramine for allergies. Recently, after assessments indicating that she is at high risk for developing breast cancer, DH’s primary care physician prescribed tamoxifen (20 mg), which is approved in the US as a risk-reducing therapy. When her pharmacist asked about any new problems related to her medications, DH noted that since starting the tamoxifen, she has been experiencing hot flashes, fatigue, and pain in her joints. Her pharmacist replied that these are relatively normal side effects associated with tamoxifen. DH then asked about the safety of taking tamoxifen with all of her other medications.

Discussion

There are 2 FDA-approved medications available in the US to reduce the risk of primary breast cancer, namely the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene. Both of these drugs reduce breast cell proliferation by inhibiting the interaction between estrogen and the estrogen receptor in breast tissue. A systematic review of published studies indicated that, assuming treatment over a 5-year period, tamoxifen and raloxifene prevent approximately 7 to 9 occurrences of estrogen-receptor-positive (ER+) breast cancer per 1,000 women-years.1 Compared with placebo, these therapies reduce the relative risk of developing ER+ breast cancer by 42% and 67%, respectively.1 In a head-to-head comparison study, however, tamoxifen and raloxifene showed no significant differences in the numbers of invasive ER+ breast cancer cases prevented.1

Typical of most medications, tamoxifen and raloxifene are not without adverse events, the most common include hot flashes, fatigue, and joint pain.1 Compared with raloxifene, tamoxifen is associated with increased risks for thromboembolitic events and cataracts. Compared with placebo, tamoxifen increases the risk of thromboembolitic events and endometrial cancer.1

Tamoxifen interacts with several classes of drugs that can alter its availability and/or efficacy. In the case study presented, DH reported experiencing some of the more common adverse events associated with tamoxifen. In addition, several drug-drug interactions were discovered during the medication therapy management visit with her pharmacist.

Tamoxifen is a prodrug that must be metabolized into the active metabolites endoxifen and 4-OH tamoxifen in order to function as an estrogen inhibitor. Tamoxifen is ultimately metabolized by the CYP2D6 enzyme in the cytochrome P450 enzyme family. Therefore, any drugs that interfere with the cytochrome P450 family or inhibit the activity of CYP2D6 can reduce the conversion of tamoxifen to its active metabolites. These interacting drugs can ultimately decrease the efficacy of tamoxifen in reducing the risk of primary breast cancer. Several classes of drugs can inhibit CYP2D6 activity, including antidepressants such as fluoxetine, paroxetine, sertraline, and bupropion; antihistamines such as diphenhydramine; heart rhythm medications such as quinidine and amiodarone; and HIV/AIDS medications.

Based on evidence for these interactions, the pharmacist in this case study identified the problem that DH’s fluoxetine and diphenhydramine may interact with her tamoxifen. The pharmacist called DH’s physician to discuss alternative medications. As a result of this discussion and the pharmacist’s advice, the physician prescribed venlafaxine (75 mg) for depression and loratadine for allergies. These alternatives for fluoxetine and diphenhydramine, respectively, do not interact with cytochrome P450 family members and therefore do not affect the functionality of tamoxifen. As this case study shows, alternative medication options are available to help avoid drug-drug interactions with tamoxifen.